Modeling Hippocampal CA1 Gabaergic Synapses of Audiogenic Rats

Rodrigo F.O. Pena, Cesar Celis Ceballos, Júnia Lara De Deus, Antonio Carlos Roque, Norberto Garcia-Cairasco, Ricardo Maurício Leão, Alexandra Olimpio Siqueira Cunha

Research output: Contribution to journalArticlepeer-review

Abstract

Wistar Audiogenic Rats (WARs) are genetically susceptible to sound-induced seizures that start in the brainstem and, in response to repetitive stimulation, spread to limbic areas, such as hippocampus. Analysis of the distribution of interevent intervals of GABAergic inhibitory postsynaptic currents (IPSCs) in CA1 pyramidal cells showed a monoexponential trend in Wistar rats, suggestive of a homogeneous population of synapses, but a biexponential trend in WARs. Based on this, we hypothesize that there are two populations of GABAergic synaptic release sites in CA1 pyramidal neurons from WARs. To address this hypothesis, we used a well-established neuronal computational model of a CA1 pyramidal neuron previously developed to replicate physiological properties of these cells. Our simulations replicated the biexponential trend only when we decreased the release frequency of synaptic currents by a factor of six in at least 40% of distal synapses. Our results suggest that almost half of the GABAergic synapses of WARs have a drastically reduced spontaneous release frequency. The computational model was able to reproduce the temporal dynamics of GABAergic inhibition that could underlie susceptibility to the spread of seizures.

Original languageEnglish (US)
Pages (from-to)2050022
Number of pages1
JournalInternational journal of neural systems
Volume30
Issue number5
DOIs
StatePublished - May 1 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Computer Networks and Communications

Keywords

  • CA1 pyramidal cells
  • Wistar audiogenic rats
  • inhibitory postsynaptic currents
  • interevent interval
  • release frequency

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